PFC

PFC

Epo may be out in the open but now a new doping controversy is brewing.
Pfc — Artificial blood — can carry 50 times more oxygen than real blood
and It’s undetectable. but for cyclists, it may be lethal.

story: ian austen.

The post-EPO era in cycling began late in spring last year, on a back
road in the Swiss canton of Ticino, when Mauro Gianetti slipped out of the
back of the bunch in the Tour of Romandie and waved for the race
ambulance. Gianetti was to spend the next fortnight fighting for his life
in intensive care in hospital in Lausanne.

This was the event that brought perfluoro-carbon (PFC) to the notice of
the cycling authorities. Gianetti is currently suing a Swiss doctor who
treated him in the Lausanne hospital to which he was taken, over
allegations that the drug was responsible for his illness. Gianetti
himself blames a combination of stomach trouble and dehydration.

Whatever the truth of those particular allegations, the fact is that
only a few days later, at the start of the Giro d’Italia in Nice, the
Union Cycliste Internationale issued a letter to all the teams taking part
warning them of the dangers of using PFC.

The Gianetti controversy was largely forgotten for the next couple of
months, only to resurface in the Tour de France. It was then that the
French press began talking to the men who had treated the Swiss rider –
and they remained adamant, despite Gianetti’s denials, that his illness
was due to the use of the new drug.

Others maintained that Johan Museeuw’s illness after his crash in
Paris-Roubaix last year was due to use of PFC. The 1996 world champion was
adamant in his denial.

So no-one knows for sure whether PFC is being used by professional
cyclists. There was, though, the same kind of uncertainty with EPO until
last July: that episode proved once again that in the fight against drugs
in sport, the cheats are always one step ahead of the authorities.

Just as the 1998 Tour de France doping scandal is finally forcing the
development of effective measures against EPO and other cloned hormones,
PFC is just one of a whole new range of products that may soon make EPO
and its ilk passé.

The new drugs, known as ‘artificial blood’, offer those seeking an
illicit edge all the performance enhancement of EPO without the lag time,
and at lower cost. Unfortunately, the potential for health problems among
top athletes is equally dramatic.

Human experiments for legitimate uses of one blood substitute, made by
the American drug giant Baxter, resulted in an unexpected number of
unexplained deaths – despite careful supervision and supporting
research.

The recent scares over blood tainted by HIV, CJD and other potentially
devastating diseases have sparked a rush by drug companies to create a new
form of the most vital of bodily fluids.

Without exception, all the substitutes so far in production perform the
one task that is vital for performance enhancement – they deliver oxygen
quickly to oxygen-starved muscles. None of them, though, are ambitious or
inventive enough to attempt to recreate all the other vital functions of
blood, including disease suppression and clotting.

Whatever the performance benefits, squirting fake blood into the veins
of cyclists whose bodies are already under enormous stress would seem to
be irresponsible in the extreme.

To date, only one blood substitute – PFC, the substance Gianetti is
accused of using – has attracted any substantial notice in the cycling
world. Gianetti spent the best part of a month in hospital after his
initial scare, and only came back to racing late in the season. PFC is
also the only fake blood that has so far received full approval for use on
humans. Even so Dr Laurent Rivier, head of the Institute of Legal Medicine
at the University of Lausanne, Switzerland’s IOC-approved anti-doping lab,
thinks PFC might be a waste of time and money for its illicit users. “The
riders will not tell us why they use it,” says Dr Rivier. “I am very
doubtful of its value.”

At first glance, PFC looks like a doper’s dream. To start with, it can
carry 50 times more oxygen than real blood in some circumstances.
Mind-bogglingly, that means you can fill a beaker with oxygenated PFC,
drop a mouse in it, and the mouse will stay alive even after its lungs
have filled with the liquid.

Detection of PFC using current anti-doping controls is also impossible.
It’s expelled from the body by breathing rather than being passed in
urine, and its use has no impact on red blood cell or haematocrit levels –
the current, unsatisfactory, indicator used by the UCI to monitor EPO
use.

But there is, of course, a catch. PFC is a chemical cousin of Teflon,
that slippery substance used in non-stick frying pans and chain
lubricants. So while that swimming mouse may not drown while paddling in
the beaker, it might not come out in the best of health.

PFC has been transformed into synthetic blood to try to get around that
problem, through some chemical manipulations and a degree of control over
the level of exposure that users are subject to.

Generally, PFC can only be safely used for a couple of hours in
relatively small quantities, usually between 500ml and one litre. Yet that
strips away much of its dramatic oxygen-carrying power.

Patients using Fluosol, a brand of PFC approved for use during heart
surgery, must also breath pure oxygen during surgery. Most doctors found
that process so awkward that the product was pulled from the market
because of poor sales in 1994.

Extra oxygen is also likely to be required for users of Oxycyte, an
improved version of PFC that’s likely to undergo human tests this year.
Obviously, riders are unlikely to strap on cylinders of oxygen before
heading out to sign on. And that’s why Dr Rivier is sceptical about the
value of PFC for abuse in sport. Either its abusers are taking dangerous
doses or they’re wasting their money.

“If this is something that is being used,” says Dr Rivier, “it is still
very rare.” Nevertheless, Dr Rivier’s lab, as well as the IOC’s approved
facility in Montreal, are developing methods to detect PFC.

Looking for a pure synthetic like PFC should be far easier than
detecting cloned EPO, which is largely indistinguishable from that
produced naturally by the body. By contrast, says Dr Rivier, “the body
does not produce PFC, so far as we know.”

Instead, his chief frustration is the agreement between riders and the
UCI, preventing his lab from testing riders’ blood for anything other than
haematocrit levels and other EPO-related indicators – the infamous 50 per
cent test. “We need to get access,” says Dr Rivier pointedly. That may be
coming. But it might, in any case, ultimately be irrelevant. The other
major approach to artificial blood, which is nearing the market, may make
PFC obsolete even before it catches on.

At least four companies are chasing a new plan that’s compellingly
simple: purified haemoglobin.

Haemoglobin molecules within red blood cells deliver oxygen throughout
the body. As long ago as the early ’80s, a US military project managed to
remove pure haemoglobin from the red cells. But only now has a way of
safely reintroducing modified haemoglobin into the bloodstream been
devised.

The new development has given rise to several new products; three are
currently undergoing tests on humans. They are packed into the same kind
of intravenous bags now used for regular blood, and are administered in
much the same way.

Best of all for both legitimate and illegitimate users, they are the
height of convenience. A rider with a low haematocrit count could raise it
instantly with an infusion – like adding oil to a car engine.

By comparison, EPO abuse is an extremely long and complicated process.
Because the hormone only stimulates natural red cell production, it must
be injected up to two weeks before competition. And, if deadly blood
thickening is to be avoided, dosages have to be calculated using a formula
based on body weight and a rider’s programme.

As with any new product that has doping-abuse potential, the big
question on modified haemoglobin is whether top athletes are actually
using it. Privately, a top executive at one of the modified haematocrit
makers acknowledges that there’s great potential for abuse of his product
by athletes. But Dr Rivier simply doesn’t know what, if anything, is
happening.

The only modified haematocrit approved for sale right now is made by
BioPure in Cambridge, Massachusetts, and intended for animals – although,
in theory, it could be used by illegally by humans. But even using the
human product illicitly is something that should require serious thought –
for safety reasons alone, if not for moral ones. At one time it looked as
if Baxter’s product, HemAssist, would be available for sale for human use
by now. The company had, in fact, already built a factory in Switzerland
to manufacture it.

Human trials on elective surgery patients went without a hitch. But
when the company tried the product in hospital emergency rooms on trauma
patients, such as cyclists who had been knocked down by motorists, they
started to run into problems. Three patients using the product died to
every control patient who didn’t receive it. Baxter quickly junked
HemAssist, restarted their programme by buying another company working on
a similar product, and are now figuring out what to do with that $110
million factory.

The source of the trouble is still unclear. But the leading theory is
that the products aren’t suitable for patients in shock and under severe
stress. Professional bike riders aren’t in shock, but no one would argue
that their bodies are in anything approaching a normal state during the
middle of, say, a mountain stage in the Tour de France.

Whatever the potential danger, though, it still seems likely that the
modified haemoglobin products’ ability to boost the blood oxygen with
little fuss and at relatively low cost will attract some illicit users.
But, as yet, it doesn’t appear that any IOC lab is attempting to develop a
test. Of course, this is another doping abuse that only blood testing will
establish.

But beyond that, the big problem is simply money. Despite all the
post-Tour fuss, work in Canada on a test for EPO – for which Dr Rivier’s
lab conducted field tests of riders – remains stalled because funding is
scarce for further large-scale tests on athletes. And Dr Rivier is already
struggling to fund his other projects. “We have enough difficulties
already with the PFCs,” he says, and is consequently reluctant to take
anything else on.

Dr Christiane Ayotte, head of the Institut de la Récherche
Scientifique-Santé – an IOC-approved anti-doping lab near Montreal –
believes athletes using PFC are either wasting their money or seriously
risking their health.

“It’s toxic,” she says. “We are really surprised at some substances we
find in athletes. It’s just because it’s an oxygen-carrying substance that
some guru or trainer has thought about injecting it.”

While its illicit use has not been studied, Dr Ayotte says papers on
its legitimate use suggest that non-toxic doses of PFC offer little in the
way of performance enhancement: in other words, it’s of no use to athletes
or cyclists unless they are prepared to use health-endangering quantities.

Dr Ayotte’s lab is currently developing a testing programme for PFC,
although it has encountered some bureaucratic delay in obtaining samples.
Not wishing to scaremonger, she does admit that, at the moment no-one
really has any idea about the extent of its illicit use. “It’s difficult
to know if it’s used or not. There may be only one case.”

She is certainly worried, though, about the potential for abuse offered
by the modified haemoglobin drugs: “I may be getting cynical but this
seems to be the way sport is going.” Her fear is of a possible series of
deaths from blood clots in otherwise healthy athletes.

As usual, the acid test of whether cycling and other sports are serious
about controlling the escalation of doping will come down to putting hard
cash behind the hand-wringing and pious promises.

Artificial blood is just one example of a medicine that has been abused
by sportsmen to enhance performance – with potentially disastrous
side-effects. But there are many others…

DHEA

Used medically to slow down the effects of ageing.

Used by sportsmen to enhance muscular development.

Side-effects: the same as other anabolic steroids – acne, migraines, nosebleeds, tendinitis, prostate cancer and, in the long term, death.

Creatine

Used medically to treat cardiac problems. Not banned, but the topic
of intense debate.

In sportsmen, increases muscle strength, often in conjunction with
anabolic steroids.

Side-effects can include liver and kidney problems.

Anticoagulants

Used medically to prevent blood clotting.

Used by sportsmen in conjunction with EPO to thin the blood. Not
banned, because on their own they do not enhance performance.

Bronchiodilators

Used widely to treat and prevent asthma. Banned if found in large
amounts.

Used by sportsmen as a stimulant because the main ingredient,
salbutamol, is similar to adrenalin, and to increase respiratory powers.

Side-effects include headaches and digestive problems if taken to
excess.

Testosterone

Administered medically to men whose testicles do not produce enough
of the hormone.

Used by sportsmen as an anabolic steroid, to increase muscular mass.
Weightlifters have been rumoured to take up to 250 times the normal
medical dose.

Side-effects include acne and low sperm count.

Trinitrin

Medical use is as a blood vessel dilator and heart stimulant to
treat and prevent angina.

Sportsmen apparently use it for explosive events as it reduces
warm-up time.

Side-effects include headaches, nausea and high blood
pressure.

For an athlete, it’s a naturally occurring hormone with an undeniably
alluring promise: more muscle, less fat. In short, it’s a substitute for
steroids that’s completely undetectable with any current anti-doping test.
But Insulin Growth Factor 1, or IGF-1, has so far attracted little of the
scrutiny heaped upon EPO since the Tour scandal.

Despite IGF-1′s low profile, no-one doubts that it’s being used in
sport. Last autumn, the doctor for the Australian national track team
acknowledged that his riders were receiving a milk product containing the
banned substance – a situation that the team insists doesn’t violate the
IOC ban on the hormone. And there’s no coyness about IGF-1 in the
bodybuilding world – it’s openly touted in magazines and on the Internet
as the next wonderdrug and a ‘natural’ alternative to steroids.

IGF-1 is a hormonal cousin of the better-known Human Growth Hormone. In
fact, in natural circumstances HGH stimulates its production within the
body. In the medical world, cloned IGF-1 is used, or being studied, for
treating dwarfism in children, some forms of diabetes, wasting in AIDS
patients and physical degeneration of people with non-functioning
pituitary glands.

Like EPO, IGF-1 evades all current anti-doping measures because it is a
clone of a naturally occurring human hormone and its levels vary wildly
even over the course of a single day.

Legality aside, does it fulfil its promise for athletes interested in a
needle-induced performance boost? Despite all the hype in the bodybuilding
world, no-one really knows for sure. Dr Christiane Ayotte, head of the
IOC-approved anti-doping lab in Canada, says the lack of recognised
research about IGF-1′s effects on athletes could mean that, as with many
drugs, its power may be grossly exaggerated.

“Sure, you can probably find some paper published in Bulgaria. But is
that a reason to inject it in athletes?” What’s more, much of what is
being sold as IGF-1 in the United States does not appear to be a clone of
the human hormone. Exactly what those products are is a mystery, as US law
excludes so-called dietary supplements from any kind of government testing
or regulatory scrutiny.

But even if it’s pure, IGF-1 has some frightening potential problems.
It can cause brain swelling, coronary artery disease and enlarged hearts,
and induce diabetic comas. There are unproven fears that prolonged use
could lead to cancers of the soft body tissues. The real stuff is also
hugely expensive, even without black market mark-ups. Medical patients in
the United States can spend up to $20,000 a year on the drug.

Don’t despair if you’re short of cash and not interested in an early
death. There is a cheap and risk-free way to boost your IGF-1 levels:
training.

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